Three-Parent IVF: Gene Replacement for the Prevention of Inherited Mitochondrial Diseases

Mitochondria are intracellular organelles that provide the necessary cellular energy supply in the form of ATP produced by oxidative phosphorylation. Mitochondrial disease can result from mtDNA mutations or nuclear DNA mutations in mitochondrial function. In addition, there is increasing evidence that acquired mtDNA mutations are involved in various chronic age-related diseases such as diabetes, cardiovascular disease and Parkinson's disease. (See comment 1)

The true prevalence of mtDNA disease is unknown. However, it is estimated that about 1 in about 4,000 children born in the United States suffer from hereditary mitochondrial disease. (2) Mitochondrial disease usually affects tissues that require high energy such as brain, muscle, liver, heart, kidney and CNS. Although these diseases are clinically heterogeneous, symptoms may include hearing loss, blindness, diabetes, muscle weakness, heart, kidney and liver failure. There are many distinct clinical syndromes. However, many patients do not belong to easily defined clinical groups.

The mitochondrial genome contains only 37 genes, but mtDNA is maternally inherited. Each cell contains several thousand copies of mtDNA. Normal individuals are allogeneic, ie all mtDNA copies are identical. However, the mitochondrial mutation may be homologous in which all copies are mutated, or heterogeneous in which the individual contains a mixture of mutant DNA and wild type DNA. Patients suffering from mtDNA disease are usually heterogeneous. Those tissues and cells have a mixture of wild type and mutant mtDNA. The clinical phenotype is dependent on the ratio of mutations to wild type mtDNA in diseased cells and tissues. There is a threshold effect, ie abnormal mtDNA level causing mtDNA disease. This threshold depends on the type and mutation of the tissue, but it is usually in the range of 60 to 90%.

The treatment options are usually limited. Therefore, proactive intervention to eliminate the possibility of propagation to the offspring of hereditary mitochondrial disease to the mother is actively sought.

In vitro fertilization resulted in an increase in three parents. The infant of three parents is a human child with three genetic parents made by a special form of IVF n, and the infant's mitochondrial DNA is from a third party. The program was originally designed to prevent mitochondrial disease. CRISPR is a genome editing tool that inserts, removes, and modifies DNA of virtually any organism. It is relatively simple, inexpensive and accurate and manufactures cells for disease research in laboratories around the world and is used for human test organisms to cultivate laboratory animals with modified DNA and shortly thereafter ing.

Currently, the IVF for 3 people is suitable for women with rare defects in mitochondrial DNA. (Can be confirmed by genetic testing.) These women have abortion and stillbirth much. Babies they give will suffer from incurable mitochondrial disease. This disease usually has a devastating effect on the heart, liver and other organs. A child can live a short period of time after birth. Most people can not be adult. So far, the only reproductive choice for these women is to use egg donors or adopt in vitro fertilization. Instead, in vitro fertilization of three parents gives these women the opportunity to lay healthy and genetically related children. Advocates of this technology says that mitochondrial defects will also be prevented from being taken over to the next generation.

Neurologist Doug Turnbull pioneered mitochondrial donation therapy at Newcastle and prevented women from spreading harmful mitochondrial DNA mutations to children. To perform this procedure, the doctor usually uses the IVF to create fertilized eggs. But instead of developing it into an embryo, remove the chromosomes of the parents and place them in eggs with genetic material removed. The embryo so produced has chromosomes of all parents, but the damaged mitochondria of the mother is replaced by the health of the donor. Newcastle doctors did not confirm that they did the procedure